Mismatch Repair Deficiency in Gliomas: A Rare Insight into Microsatellite Instability and Its Diagnostic Implications

Area of Science:

• Neuro-oncology
• Cancer genomics
• Molecular pathology

Background:

• Mismatch repair deficiency (MMRD) is a key feature of microsatellite instability (MSI), extensively studied in other cancers but less so in gliomas.
• MMR protein deficiencies (MLH1, MSH2, MSH6, PMS2) may influence glioma progression, treatment resistance, and response to immune checkpoint inhibitors.

Purpose of the Study:

• To evaluate mismatch repair (MMR) protein expression in gliomas using immunohistochemistry (IHC).
• To analyze the association of MMR protein deficiency with patient age, histological subtype, and CNS WHO tumor grade.

Main Methods:

• Retrospective analysis of 64 glioma cases.
• Immunohistochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2.
• Next-generation sequencing (NGS) for MSI and MMR gene mutations in MMR-deficient cases.

Main Results:

• MMR deficiency (MMRD) was found in 4.69% of cases, primarily isolated MSH6 loss.
• No significant associations were observed between MMRD and age, histological subtype, or WHO grade.
• NGS identified MSI in some cases, with frameshift mutations in MMR genes.

Conclusions:

• MMR deficiency is uncommon in gliomas, with MSH6 loss as the predominant finding.
• While not linked to standard clinicopathological parameters, MMRD may hold relevance in specific glioma subgroups.
• Integrating molecular diagnostics like NGS is valuable for MSI detection and guiding immunotherapy strategies in gliomas.